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. 2021:23:100529.
doi: 10.1016/j.imu.2021.100529. Epub 2021 Jan 30.

The screening and evaluation of potential clinically significant HIV drug combinations against the SARS-CoV-2 virus

Draško Tomić  1 , Davor Davidović  1 , Attila Marcel Szasz  2 , Melinda Rezeli  3 , Boris Pirkić  4 , Jozsef Petrik  5 , Vesna Bačić Vrca  6 , Vladimir Janđel  7 , Tomislav Lipić  8 , Karolj Skala  1 , Josip Mesarić  9 , Marija Milković Periša  10 , Zorislav Šojat  1 , Branka Medved Rogina  1
Affiliations

The screening and evaluation of potential clinically significant HIV drug combinations against the SARS-CoV-2 virus

Draško Tomić et al. Inform Med Unlocked. 2021.

Abstract

Spike glycoprotein is essential for the reproduction of the SARS-CoV-2 virus, and its inhibition using already approved antiviral drugs may open new avenues for treatment of patients with the COVID-19 disease. Because of that we analyzed the inhibition of SARS-CoV-2 spike glycoprotein with FDA-approved antiviral drugs and their double and triple combinations. We used the VINI in silico model of cancer to perform this virtual drug screening, showing HIV drugs to be the most effective. Besides, the combination of cobicistat-abacavir-rilpivirine HIV drugs demonstrated the highest in silico efficacy of inhibiting SARS-CoV-2 spike glycoprotein. Therefore, a clinical trial of cobicistat-abacavir-rilpivirine on a limited number of COVID-19 patients in moderately severe and severe condition is warranted.

Keywords: Antiviral drugs; COVID-19; HIV cocktail Therapy; Inhibition efficiency; SARS-CoV-2 spike glycoprotein; Virtual drug screening.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Schematic presentation of SARS-COV-2 virus, depicting its four structural proteins.
Fig. 2
Fig. 2
Calculated ΔGs of 44 small-molecule antiviral drugs with SARS-CoV-2 spike glycoprotein. A highest ΔG to the spike glycoprotein is expressed by saquinavir, and a lowest by foscarnet, a cytomegalovirus drug. The drugs for which ΔG is higher than −7.0 kcal/mol are considered to have minor or no inhibition of the SARS-CoV-2 spike glycoprotein. Exact values of ΔGs for these drugs are given in Table 1 in supplementary files.
Fig. 3
Fig. 3
Ten combinations with the highest inhibition of SARS-CoV-2 spike glycoprotein. All details of experimental results for these 10 combinations are given in Table 2, in supplementary materials.
Fig. 4
Fig. 4
Results of the relative efficacy of cobicistat-abacavir-rilpivirine cocktail against cocktails and single drugs already used to treat COVID-19, or are under investigation. Details of experimental results are given in Table 3, in supplementary materials.
See this image and copyright information in PMC

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